The immunoglobulin (Ig) gene superfamily comprises a large number of cell surface glycoproteins that share sequence homology with the V and C domains of antibody heavy and light chains. These molecules function as receptors for antigen, immunoglobulin and cytokines as well as adhesion molecules (A. F. Williams et al., Annu. Rev. Immunol. 6:381-405, 1988).
Most Ig superfamily members are relatively complex polydomain molecules containing multiple Ig V- and C-like domains (T. Hunkapiller et al., Adv. Immunol. 44:1-63, 1989). However, a subset of them have relatively simple structures containing only a single Ig domain in the extracellular region. Examples of this type of receptors are CD28 and CD8 (A. Aruffo et al., Proc. Natl. Acad. Sci. USA 84:8573-8577, 1987). Recently, CMRF-35, an novel membrane glycoprotein of the Ig gene superfamily containing a single extracellular Ig V domain, was identified by D. G. Jackson et al., Eur. J. Immunol. 22:1157-1163, 1992. CMRF-35 is exclusively detected on cells from both the myeloid and lymphoid differentiation pathways. However, expression of this gene is markedly influenced by stimulation of Icucocytes with mitogens and cytokines (A. Daish et al., Immunology 79:55-63, 1993).This suggests that CMRF-35 may be strongly associated with differentiation and proliferation of diverse leucocytes types. This indicates that these receptors have an established, proven history as therapeutic targets. Clearly there is a need for identification and characterization of further receptors which can play a role in preventing, ameliorating or correcting dysfunctions or diseases, including, but not limited to, rheumatoid arthritis (RA), multiple sclerosis (MS), psoriasis, systemic lupus erythematosus (SLE) and Inflammatory Bowel Disease (IBD).